Principal Supervisor: Dr Elizabeth Fullam - SLS
Co-supervisor: Dr Alex Cameron - SLS
PhD project title: Structure/Function studies of nutrient uptake in Mycobacterium bovis – the causative agent of bovine tuberculosis
University of Registration: Warwick
Bovine tuberculosis is a disease of global importance. It is estimated that the worldwide losses to agriculture from this disease amount to $3 billion per annum (1). Bovine TB is one of the biggest challenges currently facing cattle farmers in the UK (2).
The major causative agent of bovine tuberculosis (TB) is Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex. Bovine TB is a disease of high economic relevance within livestock farming since it directly affects animal productivity and influences the export of meat and dairy products. The overall proportion of herds in the UK testing positive for M. bovis is increasing. Hence, bovine TB is a serious cause for concern for UK livestock farming both economically and also with regard to welfare. In addition M. bovis can be transmitted to humans, resulting in human TB, predominantly through eating meat or dairy products produced from unpasteurised milk from infected animals (3) Bovine TB, therefore, also represents a risk to public health.
Although a vaccine strain exists: M. bovis BCG - its use is currently prohibited under EU law since it interferes with the current method of detection of bovine tuberculosis: the ‘test and slaughter’ strategy. This test identifies animals that give a positive skin reaction to mycobacterial antigens and those that test positive are slaughtered. It is not possible to distinguish between vaccinated and infected animals.
Therefore there is an urgent need for a better understanding of this pathogen. We currently do not understand how M. bovis obtains its nutrients and survives and establishes infection in cows (4). This PhD project aims to address this highly topical issue.
The aim of the project is to understand how M. bovis obtains and exploits essential nutrients. This will enable us to gain a better understanding of how this organism survives and establishes infection in cattle and will allow us to develop tools and techniques for diagnosis purposes. In this project we want to determine how M. bovis obtains and exploits essential nutrients - with the ambitious aim of determining the essentiality of these uptake systems and determining the structure, function and mechanisms of these transport systems. These studies will provide key structural and mechanistic information on nutrient transport of this pathogen. This research has clear potential to impact on the agricultural industry with biotechnological applications. ￼￼
- T. Garnier et al., The complete genome sequence of Mycobacterium bovis. PNAS 100, 7877 (Jun 24, 2003).
- P. D. Davies, Tuberculosis in humans and animals: are we a threat to each other? J. R. Soc. Med. 99, 539 (Oct, 2006).
- M. Niederweis, Nutrient acquisition by mycobacteria. Microbiology 154, 679 (Mar, 2008).
BBSRC Strategic Research Priority: Food security
Techniques that will be undertaken during the project:
Techniques will include bioinformatics and microbiology approaches (gene knockout/overexpression studies/proteomics) alongside biochemical studies of proteins identified in key nutrient uptake processes (including protein expression and purification, X-ray crystallography, biophysical techniques including isothermal calorimetry and surface plasmon resonance).
Contact: Dr Elizabeth Fullam, University of Warwick